Doktorsavhandling, 2009

Aspergilli represent a group of filamentous fungi that plays a key role in industrial
biotechnology, and as human, animal and plant pathogens. Here three Aspergillus species,
namely Aspergillus oryzae, Aspergillus niger and Aspergillus nidulans are considered. These
three species serve as working horses in industrial production of enzymes and chemicals and
as key models for basic scientific work. Due to their wide applications, it is valuable to gain
understanding of their metabolism, regulation and evolution with respect to genotypes and
phenotypes, as this may lead to improved industrial fermentation processes for desired
product formation (e.g. enzymes). We therefore applied three approaches for this
investigation, namely SYStems biology, BIoinformatics and OMICS analysis
(SYSBIOMICS). Firstly, we developed BIoinformatics methods to improve the genome
annotation of A. oryzae and this improved annotation was used to reconstruct a high quality
genome-scale metabolic network that could be used for mathematical modeling of the
physiology and for OMICS data integration, which are the core of SYStems biology.
Secondly, we designed a tri-Aspergillus DNA microarray chip to monitor the global
regulation response at the transcriptional level. This DNA chip has been exploited to reveal
conserved regulatory responses through evolution in the three aspergilli in response to change
in carbon source. This resulted in mapping of key regulatory points of metabolism in these
fungi, and it showed that SYSBIOMICS analysis of transcriptional data can lead to
reconstruction of how carbon metabolism is regulated. Lastly, we also applied the
SYSBIOMICS concept to identify possible key players/targets associated with protein
production in a high producing strain of A. oryzae. This analysis may enable diagnosis and
improvement of industrial process of protein production. In conclusion, through a number of
studies, it has been demonstrated in this thesis that SYSBIOMICS can find wide applications
in industrial biotechnology and assist in improving industrial process required for sustainable
production of enzymes and chemicals in the future.